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Isaeva E.,Neuroscience Center at Dartmouth | Isaeva E.,Bogomoletz Institute of Physiology | Hernan A.,Neuroscience Center at Dartmouth | Isaev D.,Neuroscience Center at Dartmouth | And 2 more authors.
Annals of Neurology | Year: 2012

Objective: An epileptic seizure is frequently the presenting sign of intracerebral hemorrhage (ICH) caused by stroke, head trauma, hypertension, and a wide spectrum of disorders. However, the cellular mechanisms responsible for occurrence of seizures during ICH have not been established. During intracerebral bleeding, blood constituents enter the neuronal tissue and produce both an acute and a delayed effect on brain functioning. Among the blood components, only thrombin has been shown to evoke seizures immediately after entering brain tissue. In the present study, we tested the hypothesis that thrombin increases neuronal excitability in the immature brain through alteration of voltage-gated sodium channels. Methods: The thrombin effect on neuronal excitability and voltage-gated sodium channels was assessed using extracellular and intracellular recording techniques in the hippocampal slice preparation of immature rats. Results: We show that thrombin increased neuronal excitability in the immature hippocampus in an N-methyl-D-aspartate-independent manner. Application of thrombin did not alter transient voltage-gated sodium channels and action potential threshold. However, thrombin significantly depolarized the membrane potential and produced a hyperpolarizing shift of tetrodotoxin-sensitive persistent voltage-gated sodium channel activation. This effect of thrombin was attenuated by application of protease-activated receptor-1 and protein kinase C antagonists. Interpretation: Our data indicate that thrombin amplifies the persistent voltage-gated sodium current affecting resting membrane potential and seizure threshold at the network level. Our results provide a novel explanation as to how ICH in newborns results in seizures, which may provide avenues for therapeutic intervention in the prevention of post-ICH seizures. Copyright © 2012 American Neurological Association.

News Article | December 27, 2016
Site: www.eurekalert.org

The Biophysical Society has announced the winners of its international travel grants to attend the Biophysical Society's 61st Annual Meeting in New Orleans, February 11-15, 2017. The purpose of these awards is to foster and initiate further interaction between American biophysicists and scientists working in countries experiencing financial difficulties. Recipients of this competitive award are chosen based on scientific merit and their proposed presentation at the meeting. They will be honored at a reception on Sunday, February 12 at the Ernest N. Morial Convention Center. The 2017 recipients of the International Travel Award, along with their institutional affiliation and abstract title, are listed below. Ana F. Guedes, Institute of Molecular Medicine, Portugal, ATOMIC FORCE MICROSCOPY AS A TOOL TO EVALUATE THE RISK OF CARDIOVASCULAR DISEASES IN PATIENTS. Karishma Bhasne Mohali, Indian Institute of Science Education and Research (IISER), A TALE OF TWO AMYLOIDOGENIC INTRINSICALLY DISORDERED PROTEINS: INTERPLAY OF TAU AND α-SYNUCLEIN. Chan Cao, East China University of Science and Technology, DIRECT IDENTIFICATION OF ADENINE, THYMINE, CYTOSINE AND GUANINE USING AEROLYSIN NANOPORE. Venkata Reddy Chirasani, Indian Institute of Technology Madras, LIPID TRANSFER MECHANISM OF CETP BETWEEN HDL AND LDL: A COARSEGRAINED SIMULATION STUDY. Assaf Elazar, Weizmann Institute of Science, Israel, DECIPHERING MEMBRANE PROTEIN ENERGETICS USING DEEP SEQUENCING; TOWARDS ROBUST DESIGN AND STRUCTURE PREDICTION OF MEMBRANE PROTEINS. Manuela Gabriel, University of Buenos Aires, Argentina, 3D ORBITAL TRACKING OF SINGLE GOLD NANOPARTICLES: A NEW APPROACH TO STUDY VESICLE TRAFFICKING IN CHROMAFFIN CELLS. Farah Haque National Centre for Biological Sciences, India, A NEW HUMANIZED MOUSE MODEL FOR STUDYING INHERITED CARDIOMYOPATHIC MUTATIONS IN THE MYH7 GENE. Stephanie Heusser, Stockholm University, Switzerland, STRUCTURAL AND FUNCTIONAL EVIDENCE FOR MULTI-SITE ALLOSTERY MEDIATED BY GENERAL ANESTHETICS IN A MODEL LIGAND-GATED ION CHANNEL. Amir Irani, Massey University, New Zealand, HOMOGALACTURONANS ILLUMINATE THE ROLE OF COUNTERION CONDENSATION IN POLYELECTROLYTE TRANSPORT. Olfat Malak, University of Nantes, France, HIV-TAT INDUCES A DECREASE IN IKR AND IKS VIA REDUCTION IN PHOSPHATIDYLINOSITOL-(4,5)-BISPHOSPHATE AVAILABILITY. CONFORMATIONAL TRANSITION AND ASSEMBLY OF E.COLI CYTOLYSIN A PORE FORMING TOXIN BY SINGLE MOLECULE FLUORESCENCE. Sabrina Sharmin, Shizuoka University, Japan, EFFECTS OF LIPID COMPOSITIONS ON THE ENTRY OF CELL PENETRATING PEPTIDE OLIGOARGININE INTO SINGLE VESICLES. Xin Shi, East China University of Science and Technology, DIRECT OBSERVATION OF SINGLE BIOPOLYMER FOLDING AND UNFOLDING PROCESS BY SOLIDSTATE NANOPORE. Omar Alijevic, University of Lausanne, Switzerland, ANALYSIS OF GATING OF ACID-SENSING ION CHANNELS (ASICS) UNDER RAPID AND SLOW PH CHANGES. Swapna Bera, Bose Institute, India, BIOPHYSICAL INSIGHTS INTO THE MEMBRANE INTERACTION OF THE CORE AMYLOID-FORMING Aβ40 FRAGMENT K16-K28 AND ITS ROLE IN THE PATHOGENESIS OF ALZHEIMER'S DISEASE. Anais Cassaignau, University College London, United Kingdom, STRUCTURAL INVESTIGATION OF AN IMMUNOGLOBULIN DOMAIN ON THE RIBOSOME USING NMR SPECTROSCOPY. Bappaditya Chandra, Tata Institute of Fundamental Research, India, SECONDARY STRUCTURE FLIPPING CONNECTED TO SALT-BRIDGE FORMATION CONVERTS TOXIC AMYLOID-β40 OLIGOMERS TO FIBRILS. Gayathri Narasimhan, Cinvestav, Mexico, ANTIHYPERTROPHIC EFFECTS OF DIAZOXIDE INVOLVES CHANGES IN MIR-132 EXPRESSION IN ADULT RAT CARDIOMYCYTES. Giulia Paci, European Molecular Biology Laboratory, Germany, FOLLOWING A GIANT'S FOOTSTEPS: SINGLE-PARTICLE AND SUPER-RESOLUTION APPROACHES TO DECIPHER THE NUCLEAR TRANSPORT OF HEPATITIS B VIRUS CAPSIDS. Bizhan Sharopov, Bogomoletz Institute of Physiology National Academy of Sciences of Ukraine, DISSECTING LOCAL AND SYSTEMIC EFFECTS OF TRPV1 ON BLADDER CONTRACTILITY IN DIABETES. Chao Sun, East China Normal University, FUNCTION OF BACTERIORUBERIN IN ARCHAERHODOPSIN 4, FROM EXPRESSION TO CHARACTERIZATION. Matthew Batchelor, University of Leeds, United Kingdom STRUCTURAL DYNAMICS IN THE MYOSIN 7A SINGLE α-HELIX DOMAIN. Daniel Havelka, Czech Academy of Sciences, MICROVOLUME DIELECTRIC SPECTROSCOPY AND MOLECULAR DYNAMICS OF AMINO ACIDS. Ivan Kadurin, University College London, United Kingdom, INVESTIGATION OF THE PROTEOLYTIC CLEAVAGE OF α2δ SUBUNITS: A MECHANISTIC SWITCH FROM NHIBITION TO ACTIVATION OF VOLTAGE-GATED CALCIUM CHANNELS? Linlin Ma, University of Queensland, Australia, NOVEL HUMAN EAG CHANNEL ANTAGONISTS FROM SPIDER VENOMS. Ivana Malvacio, University of Cagliari, Italy, MOLECULAR INSIGHTS ON THE RECOGNITION OF SUBSTRATES BY THE PROMISCUOUS EFFLUX PUMP ACRB. Cristina Moreno Vadillo, Cardiovascular Research Institute Maastricht, Netherlands, RESTORING DEFECTIVE CAMP-DEPENDENT UPREGULATION IN LONG-QT SYNDROME TYPE-1 THROUGH INTERVENTIONS THAT PROMOTE IKS CHANNEL OPENING. Melanie Paillard, Claude Bernard University Lyon 1, France, TISSUE-SPECIFIC MITOCHONDRIAL DECODING OF CYTOPLASMIC CA2+ SIGNALS IS CONTROLLED BY THE STOICHIOMETRY OF MICU1/2 AND MCU. Mohammed Mostafizur Rahman, Institute for Stem Cell Biology and Regenerative Medicine, India, STRESS-INDUCED DIFFERENTIAL REGULATION LEADS TO DECOUPLING OF THE ACTIVITY BETWEEN MPFC AND AMYGDALA. Marcin Wolny, University of Leeds, United Kingdom, DESIGN AND CHARACTERIZATION OF LONG AND STABLE DE NOVO SINGLE α-HELIX DOMAINS. Elvis Pandzic, University of New South Wales, Australia, VELOCITY LANDSCAPES RESOLVE MULTIPLE DYNAMICAL POPULATIONS FROM FLUORESCENCE IMAGE TIME SERIES. The Biophysical Society, founded in 1958, is a professional, scientific Society established to encourage development and dissemination of knowledge in biophysics. The Society promotes growth in this expanding field through its annual meeting, monthly journal, and committee and outreach activities. Its 9000 members are located throughout the U.S. and the world, where they teach and conduct research in colleges, universities, laboratories, government agencies, and industry. For more information on these awards, the Society, or the 2017 Annual Meeting, visit http://www.

Fedorenko O.A.,Bogomoletz Institute of Physiology | Fedorenko O.A.,State Key Laboratory of Molecular and Cellular Biology | Marchenko S.M.,Bogomoletz Institute of Physiology | Marchenko S.M.,State Key Laboratory of Molecular and Cellular Biology
Hippocampus | Year: 2014

Rise in Ca2+ concentration in the nucleus affects gene transcription and has been implicated in neuroprotection, transcription-dependent neuronal plasticity, and pain modulation, but the mechanism of regulation of nuclear Ca2+ remains poorly understood. The nuclear envelope is a part of the endoplasmic reticulum and may be one of the sources of nuclear Ca2+. Here, we studied ion channels in the nuclear membrane of hippocampal neurons using the patch-clamp technique. We have found that the nuclear membrane of CA1 pyramidal and dentate gyrus granule (DG), but not CA3 pyramidal neurons, was enriched in functional inositol 1,4,5-trisphosphate receptors/Ca2+-release channels (IP3Rs) localized mainly in the inner nuclear membrane. A single nuclear ryanodine receptor (RyR) has been detected only in DG granule neurons. Nuclei of the hippocampal neurons also expressed a variety of spontaneously active cation and anion channels specific for each type of neuron. In particular, large-conductance ion channels selective for monovalent cations (LCC) were coexpressed with IP3Rs. These data suggest that: (1) the nuclear membranes of hippocampal neurons contain distinct sets of ion channels, which are specific for each type of neuron; (2) IP3Rs, but not RyRs are targeted to the inner nuclear membrane of CA1 pyramidal and DG granule, but they were not found in the nuclear membranes of CA3 pyramidal neurons; (3) the nuclear envelope of these neurons is specialized to release Ca2+ into the nucleoplasm which may amplify Ca2+ signals entering the nucleus from the cytoplasm or generate Ca2+ transients on its own; (4) LCC channels are an integral part the of Ca2+-releasing machinery providing a route for counterflow of K{cyrillic}+ and thereby facilitating Ca2+ movement in and out of the Ca2+ store. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Harhun M.I.,St George's, University of London | Harhun M.I.,Bogomoletz Institute of Physiology
Cell Calcium | Year: 2015

Vasomotion is the rhythmical changes in vascular tone of various blood vessels. It was proposed that in rabbit portal vein (RPV) the spontaneous contractile activity is driven by vascular interstitial cells (VICs), since RPV VICs generate rhythmical changes in intracellular Ca2+ concentration ([Ca2+]i) associated with membrane depolarisation in these cells. In this work, using confocal imaging in Fluo-3 loaded RPV VICs we studied if generation of rhythmical [Ca2+]i changes is affected when Ca2+ handling by mitochondria is compromised. We also visualised mitochondria in VICs using Mito Tracker Green fluorescent dye.Our results showed that freshly dispersed RPV VICs generated rhythmical [Ca2+]i oscillations with a frequency of 0.2-0.01Hz. Imaging of VICs stained with Mito Tracker Green revealed abundant mitochondria in these cells with a higher density of the organelles in sub-plasmalemmar region compared to the central region of the cell. Oligomycin, an ATP synthase inhibitor, did not affect the amplitude and frequency of rhythmical [Ca2+]i oscillations. In contrast, two uncoupling agents, carbonylcyanide-3-chlorophenylhydrazone (CCCP) and carbonylcyanide-4-trifluoromethoxyphenylhydrazone (FCCP) effectively abolished rhythmical [Ca2+]i changes with simultaneous increase in basal [Ca2+]i in RPV VICs.These data suggest that in RPV VICs mitochondrial Ca2+ handling is important for the generation of rhythmical [Ca2+]i changes which underlie the spontaneous rhythmical contractile activity in this vessel. © 2015 Elsevier Ltd.

Harhun M.I.,St George's, University of London | Povstyan O.V.,St George's, University of London | Povstyan O.V.,Bogomoletz Institute of Physiology | Albert A.P.,St George's, University of London | Nichols C.M.,St George's, University of London
Stroke | Year: 2014

BACKGROUND AND PURPOSE - : Current knowledge states that vasoconstrictor responses to ATP are mediated by rapidly desensitizing ligand-gated P2X1 receptors in vascular smooth muscle cells (VSMCs). However, ATP is implicated in contributing to pathological conditions involving sustained vasoconstrictor response such as cerebral vasospasm. The purpose of this study is to test the hypothesis that the stimulation of VSMC P2XR receptors (P2XRs) contributes to ATP-evoked sustained vasoconstrictions in rat middle cerebral arteries (RMCAs). METHODS - : Reverse transcription- polymerase chain reaction, Western blot, and immunocytochemistry were used to analyze expression of mRNA and proteins in RMCAs VSMCs. Ionic currents and calcium responses were investigated using patch-clamp and confocal imaging techniques, respectively. Functional responses were confirmed using wire myography. RESULTS - : Expression of mRNA and protein for P2X1R and P2X4R subunits was identified in RMCA VSMCs. Confocal imaging in fluo-3-loaded VSMCs showed that ATP and a selective P2XR agonist, αβmeATP, evoked similar dose-dependent increases in [Ca]i. Patch-clamp experiments identified 2 components of P2XR-mediated currents: consisting of a fast desensitizing phase mediated by homomeric P2X1Rs and a slowly desensitizing phase involving heteromeric P2X1/4Rs. Isometric tension measurements showed that 80%:20% of initial ATP-evoked vasoconstriction in RMCA is mediated by homomeric P2X1Rs and heteromeric P2X1/4Rs, respectively. The sustained slowly desensitizing and rapidly recovering from desensitization responses are mediated by heteromeric P2X1/4Rs. CONCLUSIONS - : This study reveals for the first time that apart from rapidly desensitizing homomeric P2X1Rs, heteromeric P2X1/4Rs contribute to the sustained component of the purinergic-mediated vasoconstriction in RMCA. Our study, therefore, identifies possible novel targets for therapeutical intervention in cerebral circulation. © 2014 American Heart Association, Inc.

Tsupykov O.,Bogomoletz Institute of Physiology | Tsupykov O.,State Institute of Genetic and Regenerative Medicine
Microscopy Research and Technique | Year: 2015

Despite the great number of studies devoted to neural stem/progenitor cell biology, the ultrastructural characteristics of these cells in vitro have not been fully studied. To determine the fine structure of hippocampal neural progenitor cells (NPCs) in culture, mouse fetal hippocampi (E18) were extracted, dissected, and cells were expanded as adherent monolayer culture. Electron microscopy revealed that NPCs had an immature phenotype, with a high nuclear/cytoplasmic ratio, small and scant organelles, underdeveloped endoplasmic reticulum, and many free ribosomes and polysomes. Our results may contribute to a better understanding of the fine structure and physiology of hippocampal NPCs in vitro. © 2014 Wiley Periodicals, Inc.

Stepanyuk A.,Bogomoletz Institute of Physiology
Biologically Inspired Cognitive Architectures | Year: 2015

The grid cells (GCs) of the medial entorhinal cortex (MEC) and place cells (PCs) of the hippocampus are assumed to be the key elements of the brain network for the metric representation of space. Existing theoretical models of GC network rely on specific hypotheses about the network connectivity patterns. How these patterns could be formed during the network development is not fully understood. It was previously suggested, within the feedforward network models, that activity of PCs could provide the basis for development of GC-like activity patterns. Supporting this hypothesis is the finding that PC activity remains spatially stable after disruption of the GC firing patterns and that the grid fields almost disappear when hippocampal cells are deactivated. Here a new theoretical model of this type is proposed, allowing for grid fields formation due to synaptic plasticity in synapses connecting PCs in hippocampus with neurons in MEC. Learning of the hexagonally symmetric fields in this model occurs due to complex action of several simple biologically motivated synaptic plasticity rules. These rules include associative synaptic plasticity rules similar to BCM rule, and homeostatic plasticity rules that constrain synaptic weights. In contrast to previously described models, a short-term navigational experience in a novel environment is sufficient for the network to learn GC activity patterns. We suggest that learning on the basis of simple and biologically plausible associative synaptic plasticity rules could contribute to the formation of grid fields in early development and to maintenance of normal GCs activity patterns in the familiar environments. © 2015 Elsevier B.V. All rights reserved.

Skibo G.G.,Bogomoletz Institute of Physiology
Vitamins and hormones | Year: 2010

Brain plasticity describes the potential of the organ for adaptive changes involved in various phenomena in health and disease. A substantial amount of experimental evidence, received in animal and cell models, shows that a cascade of plastic changes at the molecular, cellular, and tissue levels, is initiated in different regions of the postischemic brain. Underlying mechanisms include neurochemical alterations, functional changes in excitatory and inhibitory synapses, axonal and dendritic sprouting, and reorganization of sensory and motor central maps. Multiple lines of evidence indicate numerous points in which the process of postischemic recovery may be influenced with the aim to restore the full capacity of the brain tissue injured by an ischemic episode. Copyright 2010 Elsevier Inc. All rights reserved.

Iegorova O.,Bogomoletz Institute of Physiology | Fisyunov A.,Bogomoletz Institute of Physiology | Krishtal O.,Bogomoletz Institute of Physiology
Neuroscience Letters | Year: 2010

P-type calcium channels play a key role in the synaptic transmission between mammalian central neurons since a major part of calcium entering pre-synaptic terminals is delivered via these channels. Using conventional whole-cell patch clamp techniques we have studied the effect of μ-opioids on P-type calcium channels in acutely isolated Purkinje neurons from rat cerebellum. The selective μ-opioid agonist DAMGO (10nM) produced a small, but consistent facilitation of current through P-type calcium channels (10±1%, n=27, p<0.001). The effect of DAMGO was rapid (less than 10s) and fully reversible. This effect was both concentration and voltage-dependent. The EC50 for the effect of DAMGO was 1.3±0.4nM and the saturating concentration was 100nM. The endogenous selective agonist of μ-opioid receptors, endomorphin-1 demonstrated similar action. Intracellular perfusion of Purkinje neurons with GTPγS (0.5mM) or GDPβS (0.5mM), as well as strong depolarizing pre-pulses (+50mV), did not eliminate facilitatory action of DAMGO on P-channels indicating that this effect is not mediated by G-proteins. Furthermore, the effect of DAMGO was preserved in the presence of a non-specific inhibitor of PKA and PKC (H7, 10μM) inside the cell. DAMGO-induced facilitation of P-current was almost completely abolished by the selective μ-opioid antagonist CTOP (100nM). These observations indicate that μ-type opioid receptors modulate P-type calcium channels in Purkinje neurons via G-protein-independent mechanism. © 2010 Elsevier Ireland Ltd.

Krishtal O.,Bogomoletz Institute of Physiology
Neuropharmacology | Year: 2015

The history of ASICs began in 1980 with unexpected observation. The concept of highly selective Na(+) current gated by specific receptors for protons was not easily accepted. It took 16 years to get these receptor/channels cloned and start a new stage in their investigation. "The receptor for protons" became ASIC comprising under this name a family of receptor/channels ubiquitous for mammalian nervous system, both peripheral and central. The role of ASICs as putative nociceptors was suggested almost immediately after their discovery. This role subsequently was proven in many forms of pain-related phenomena. Many other functions of ASICs have been also found or primed for speculations both in physiology and in disease. Despite the width of field and strength of efforts, numerous basic questions are to be answered before we understand how the local changes in pH in the nervous tissue transform into electric and messenger signaling via ASICs as transducers. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'. Copyright © 2015. Published by Elsevier Ltd.

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